Ubiquilin2, is a protein that abnormally accumulates in many neurodegenerative diseases. Additionally, mutations in UBQLN2 gene cause a familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Normally, ubiqilin2 aids the clearance of aged or damaged proteins. In case of ubiqilin2 aggregation, the cellular surveillance that targets protein clearance may be compromised, in turn causing protein accumulation. Additionally, the aggregated state of ubiqilin2 may become toxic, thus accelerating cellular death. Studies of the native and aggregation state of ubiqilin2 can give insights into protein’s function and disease mechanism. For the purpose we apply a combination of biophysical to cellular methods.

Hexanucleotide repeat expansions in C9orf72 are the most common inherited cause of ALS and FTD. This mutation elicits toxicity in part through repeat-associated non-AUG (RAN) translation of the intronic (GGGGCC)n sequence into dipeptide repeat containing proteins (DPRs). In collaboration with the neurodegenerative disease group in the Department of Neurology, we established a strong correlation between peptide structure and toxicity. At present we focus at structural studies of the toxic aggregates. The goal is to use these structures for developing molecules that reduce the formation of the toxic species .

Human genetics, cellular biology and biochemistry, and neurobiology indicate a causal role for the protein α-synuclein in the pathogenesis of Parkinson's disease (PD). Lewy bodies (LB), which consist primarily of aggregated α-synuclein, are found in patients with PD and Lewy body dementia (DLB). In addition, α-synuclein accumulates in glial cells in condition known as multiple system atrophy (MSA). The abnormal accumulation of α-synuclein is now recognized as a signature of multiple forms of neurodegeneration. Yet our understanding of the molecular mechanism of aggregation is still limited. To increase our knowledge in the area, we currently focus on the studying the structure of α-synuclein fibrils which were purified from the brains of the individuals affected by PD, DLB and MSA.